This proposal will develop and evaluate an innovative and potential clinical treatment for asthma. Although there are a multitude of different possible triggers, an acute asthmatic attack is always characterized by contraction of the smooth muscle in the airway wall. Despite this common end point, most of the clinical asthma research and therapies in recent years have focused on understanding the immunologic factors that often lead to asthmatic attacks. The present proposal describes research and development that focuses on a treatment of smooth muscle that will thus be effective in asthmatic attacks regardless of the initial trigger. It involves the design, construction, and application of a biomedical device that can prevent or minimize the ability of the smooth muscle in the airways to constrict. The project involves a close working partnership between the physiologic laboratories and expertise at the Johns Hopkins University and a small California biomedical engineering company, that is providing the mechanical and bioengineering skills needed for product development. The overall hypothesis governing this proposal is that, the treatment of airway smooth muscle with this innovative system will minimize obstruction caused by smooth muscle contraction, regardless of its origin. In this proposal, six specific aims will be directed toward addressing this hypothesis. Two aims are concerned with determining the optimal parameters and design criteria for maximal effectiveness, and four aims are concerned with assessing the safety and potential side effects of this treatment. The information obtained from these functional studies will be essential, not only in the ongoing engineering and development of the optimal device, but also to help set guidelines for the use of this device in future clinical trials. The studies proposed in this BRP will thus allow optimization of a biomedical device that has the potential to effectively cure all forms of human asthma.